The field of this invention is the area of molecular biology, in particular as related to recombinant expression of an acetyltransferase of Serogroup A Neisseria meningitidis, and immunogenic compositions, especially immunogenic compositions comprising fully acetylated capsule of Neisseria meningitidis, Serogroup A.
Neisseria meningitidis is a leading worldwide cause of meningitis and rapidly fatal sepsis in otherwise health individuals (Apicella, M. A. (1995) in Principles and Practice of Infectious Diseases, eds. Mandell, G. L., Douglas, R. G., and Bennett, J. E., Churchill Livingstone, New York, pp. 1896-1909). In excess of 350,000 cases of meningococcal disease were estimated to have occurred in 1995 (WHO Report (1996) WHO, Geneva, ISBN 92 4 1561823). The problem of meningococcal disease is emphasized by the recurrence of major epidemics due to serogroups A, B, and C N. meningitidis over the last 20 years, such as: the devastating serogroup A outbreak in sub-Saharan Africa in 1996 (WHO (1996) Meningitis in Africa. The constant challenge of epidemics. WHO 21:15 March); the recent dramatic increases in the incidence of serogroup B and C meningococcal disease in parts of North America (CDC (1995) MMWR 44:121-134; Jackson, L. A. et al. (1995) JAMA 273:390-394; Wahlen, C. M. et al. (1995) JAMA 273:383-389); and the emergence in Europe and elsewhere of meningococci with decreased susceptibility to antibiotics (Campos, J. et al. (1992) J. Infect. Dis. 166:173-177).
Differences in capsular polysaccharide chemical structure determine the meningococcal serogroups (Liu, T. Y. et al. (1971) J. Biol. Chem. 246:2849-58; Liu, T. Y. et al. (1971) J. Biol. Chem. 246:4703-12). Meningococci of serogroups B, C, Y, and W-135 express capsules composed entirely of polysialic acid or sialic acid linked to glucose or galactose (Liu, T. Y. et al. (1971) J. Biol. Chem. 246:4703-12; Bhattacharjee, A. K. et al. (1976) Can. J. Biochem. 54:1-8), while the capsule of group A N. meningitidis is composed of N-acetyl mannosamine-1-phosphate (Liu, T. Y. et al. (1971) J. Biol. Chem. 246:2849-58). The currently available capsular polysaccharide vaccines for serogroups A, C, Y, or W-135 N. meningitidis are effective for control of meningococcal outbreaks in older children and adults. However, because of poor immunogenicity in young children and short-lived immunity (Zollinger, W. D. and Moran, E. (1991) Trans. R. Soc. Trop. Med. Hyg. 85:37-43), these vaccines are not routinely used for long-term prevention of meningococcal disease.
In some epidemic settings, simultaneous or closely-linked meningococcal outbreaks have occurred in the same population due to different serogroups (Sacchi, C. T. et al. (1994) J. Clin. Microbiol. 32:1783-1787; CDC (1995) MMWR 44:121-134; Krizova, P. and Musilek, M. (1994) Centr. Eur. J. Publ. Hlth 3:189-194). Further, Caugant et al. (Caugant, D. A. et al. (1986) Proc. Natl. Acad. Sci. USA 83:4927-4931; Caugant, D. A. et al. (1987) J. Bacteriol. 169:2781-2792) and others have noted that meningococcal isolates of different serogroups may be members of the same enzyme type (ET)-5, ET-37 or ET-4 clonal complexes.
Neisseria meningitidis serogroup A is responsible for the massive epidemics of meningococcal meningitis and septicemia that periodically affect sub-Saharan Africa, China, South America and other parts of the world. The serogroup A capsular polysaccharide (CPS) that confers serogroup specificity is composed of repeating units of (α1→6) linked N-acetyl-D-mannosamine-1-phosphate that is O-acetylated (1). Although there is evidence of other glycosidic linkages (2), the principal linkage between monomer ManNAc residues in this polysaccharide is the (α1→6) phosphodiester bond involving the hemiacetal group of carbon 1 and the alcohol group of carbon 6 of the mannosamine residues. Serogroup A CPS is structurally distinct from other disease-causing meningococcal serogroups B, C, Y and W-135 which are composed of, or contain sialic acid (1, 3, 4).
There is a long felt need in the art for improved immunogenic compositions useful for generating a protective immune response to Neisseria meningitidis, which is highly contagious and causes serious illness.